CV Science

Marc Humbert MD, PhD, Respiratory Medicine

Course and current status

Marc Humbert, MD, PhD, is Dean and Professor of Respiratory Medicine at the University Paris-Saclay Faculty of Medicine in Le Kremlin-Bicêtre, France. He is the Director of the Respiratory and Intensive Care Medicine Department, French Pulmonary Hypertension Reference Centre, Assistance Publique Hôpitaux de Paris. He is the Director of the Inserm / University Paris-Saclay laboratory “Pulmonary Hypertension; Pathophysiology and Novel Therapies” (Inserm UMR_S 999, HPPIT). Marc Humbert is vice-coordinator of the European Reference Network for rare and low prevalence respiratory diseases (ERN-LUNG). He is Past President of the European Respiratory Society (ERS), Chief Editor of the European Respiratory Journal (2013-2017) and Section Editor in charge of Pulmonary Vascular Medicine. Doctor Honoris Causa of the University of Medicine and Pharmacy Carol Davila (Bucarest, Romania), he has received several scientific distinctions including the 2006 ERS Cournand Lecture Award, the 2009 Descartes-Huygens Award from the Royal Netherlands Academy of Arts and Sciences, the 2016 Rare Disease Award of the Fondation de France, the 2018 ERS Award for Lifetime Achievement in Pulmonary Arterial Hypertension, the Excellence 2019 Award from the Fondation du Souffle, the 2020 American Heart Association’s 3CPR (Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation) Distinguished Achievement Award, the 2024 ERS Congress Chair Award (European Respiratory Society, Vienna), the Grand Prix of the Assistance Publique Hôpitaux de Paris Foundation (2025) and the Grand Prix  Inserm (2025). Clarivate Analytics recognizes Marc Humbert as one of the world's highly cited researchers in the field of Clinical Medicine.

Scientific summary

Pulmonary Hypertension (PH) is characterized by a persistent elevation of mean pulmonary arterial pressure (mPAP) at rest, assessed through right heart catheterization. In healthy subjects, mPAP stands at 14.0 mmHg with a standard deviation of 3.3 mmHg, thus PH is diagnosed when mPAP exceeds strictly 20 mmHg. The current classification of PH, revised during the 6th World Symposium in 2018 and refined by the European PH Guidelines, identified five groups: pulmonary arterial hypertension (Group 1), PH associated with left heart disease (group 2), PH associated with lung diseases and/or hypoxia (Group 3), PH associated with pulmonary artery obstructions (group 4), and PH with unclear and/or multi-factorial mechanisms (group 5). This classification is crucial not only for routine clinical practice but also for research units focusing on PH pathophysiology, as it enables the grouping of patients based on their pathophysiological, clinical, and therapeutic characteristics.

Pulmonary arterial hypertension (PAH, Group 1) is a cause of pre-capillary PH defined by a resting mPAP > 20 mmHg, a pulmonary vascular resistance (PVR) >2 Wood Units and a normal pulmonary artery wedge pressure ≤ 15 mmHg1,2. It differs from isolated post-capillary PH, primarily caused by left heart failure, characterized by a pulmonary artery wedge pressure > 15 mmHg and PVR ≤ 2 Wood Units. PAH can be idiopathic or caused by genetic mutations, exposure to drugs or toxins, or associated with connective tissue disease (CTD), congenital heart disease, human immunodeficiency virus, schistosomiasis, and porta hypertension (e.g., portopulmonary hypertension). The estimated prevalence of PAH in adults ranges from 15-55 cases per million, with an annual incidence of 2.4-6 per million, affecting females more frequently than males.

The fundamental pathomechanisms of PAH involve the progressive loss and obstructive narrowing of the small and medium-sized pulmonary arteries. This process significantly contributes to increased mPAP and PVR observed in PAH patients. At the Joint Research Unit UMR_S 999 (HPPIT), "PULMONARY HYPERTENSION: PATHOPHYSIOLOGY & NOVEL THERAPIES," our primary focus is centered on understanding PH pathophysiology and improving clinical management. Our central objective is to unveil the mechanisms behind pulmonary vascular remodeling and identify new molecular targets to alleviate and ultimately cure PAH and other forms of PH. Leveraging a nationwide web-based Registry, a biobank, and a team of highly competitive scientists, we have explored various molecular pathways responsible for pulmonary vascular remodeling, identified potential targets for therapy, facilitated drug development based on these targets, and assessed novel therapies. Our ultimate goal is to alleviate and cure PH while advancing innovative therapies.

We are committed to translating the novel insights into advancements in patient care. Our group comprises leading French teams in the field of PH research and care, collectively working to enhance the understanding and treatment of PAH, a severe condition with a largely underestimated impact and significant unmet needs. This collaborative Research Unit has fostered synergy between basic scientists and clinicians, providing access to a comprehensive clinical database and biobank. It has also facilitated education, medical awareness, and studies in a rapidly evolving and competitive realm of medical research.

Our strategy is rooted in the complete dedication of two large teams of researchers and clinicians specializing in pulmonary vascular research. Team 1 has conducted extensive investigations into the molecular and cellular mechanisms underlying pulmonary vascular remodeling, placing particular emphasis on the phenotypic heterogeneity of pulmonary endothelium and the specific dysfunctions in the BMP/TGF-β signaling pathway. The primary objective of this research team is to uncover novel pathways associated with PAH, pinpoint biomarkers, and explore new therapeutic avenues. Team 2 has extensively investigated the pathophysiological mechanisms associated with PH predisposing genes and ion channels remodeling and their therapeutic interests, focusing on molecular and cellular mechanisms of pulmonary vascular and cardiac remodeling in PAH. This research team's main goal is to understand the pathological mechanisms linked to genetic variation and ion channels and to identify new therapeutic options.